Single-cell analysis of the peripheral immune landscape in Parkinson's disease: insights into dendritic cell and CD4+...

Parkinson's disease (PD) is characterised by α-synuclein aggregation, dopaminergic neuron loss and chronic neuroinflammation. Disruption of the blood-brain barrier enables immune cell infiltration, including dendritic cells (DCs) and CD4+ T-cells, contributing to disease progression. To explore peripheral immune mechanisms in PD, we isolated DCs and CD4+ T-cells from the blood of 17 PD patients and 10 controls using magnetic separation, followed by flow cytometry and single-cell RNA sequencing. Cell-type annotation identified CD4+ T-cell and DC subtypes, including rare DC3 cells. PD patients showed reduced circulating DCs, with no change in CD4+ T-cell levels. Differential gene expression and pathway analysis suggest CD4+ effector memory T-cells (TEMs) and cDC2s as important mediators of immune responses in PD, enriched for immune-related pathways including T-cell activation and antigen presentation. Our findings implicate specific immune subsets in PD-associated neuroinflammation, suggesting cDC2s and CD4⁺ TEMs as potential targets for immunomodulatory strategies.